A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway

Area of Science:

• Gerontology and molecular biology research.
• Utilizes the model organism Caenorhabditis elegans for aging studies.

Background:

• Aging is associated with increased risk of diseases like cancer and neurodegeneration.
• Understanding healthy aging and developing interventions is crucial due to the growing elderly population.

Purpose of the Study:

• To identify small molecules that promote healthy aging using a high-throughput screen.
• To investigate the mechanisms by which these molecules affect aging and behavior.

Main Methods:

• High-throughput screening in Caenorhabditis elegans to identify aging-promoting compounds.
• Assessed effects of Carbamazepine and Calmagite on neurotransmitter levels, lifespan, and behaviors.
• Investigated molecular mechanisms including calcium homeostasis and transcription factor DAF-16 activity.

Main Results:

• Identified 11 small molecules promoting healthy aging, including Carbamazepine and Calmagite.
• Carbamazepine and Calmagite extended lifespan and preserved behaviors in aging C. elegans.
• These compounds improved muscle excitability and calcium homeostasis, activating DAF-16 nuclear translocation.

Conclusions:

• Carbamazepine and Calmagite enhance healthy aging by modulating neurotransmitter levels and improving physiological functions.
• The identified compounds represent potential therapeutic interventions for age-related decline.
• DAF-16 pathway activation is a key mechanism underlying the observed pro-longevity effects.